BIK在胰腺癌中的表达特征及临床预后价值OA

Objective To explore the expression pattern of Bcl-2 interacting killer protein(BIK)in pancreatic cancer,its relationship with tumor microenvironment and patient prognosis,and to evaluate its potential as a prognostic biomarker and therapeutic target.Methods(1)Expression profile data of pancreatic cancer were obtained from The Cancer Genome Atlas(TCGA)and Gene Expression Omnibus(GEO)datasets.Differentially expressed genes were screened using bioinformatics methods,and BIK was identified as the research target based on survival analysis.Furthermore,Gene Ontology(GO)enrichment analysis and the Gene Expression Profiling Interactive Analysis(GEPIA)database were used to evaluate its potential biological function and its correlation with collagen deposition and immune cell infiltration.(2)Tissue samples from 56 pancreatic cancer patients admitted to Lanzhou University Second Hospital between December 2020 and September 2023 were retrospectively collected.Hematoxylin-eosin(HE),immunohistochemistry(IHC),and Sirius red staining were performed to assess the correlation between BIK expression and patients'clinicopathological features as well as prognosis.Results BIK was significantly overexpressed in pancreatic cancer tissues and associated with poor prognosis(P<0.05).It was enriched in extracellular matrix regions containing collagen and positively correlated with the expression of collagen type Ⅳ alpha 1 chain(COL4A1)and lysyl oxidase(LOX)(r=0.39,0.23,P<0.001).BIK expression was significantly inversely correlated with M1 macrophage infiltration(r=-0.166,P<0.001),but showed a significant positive correlation with the expression of immunosuppressive markers TGFB1 and TGFB2(r=0.53,0.26,P<0.001).High BIK expression was an independent risk factor affecting the overall survival(OS)in pancreatic cancer patients(P=0.0014),and it was closely correlated with the proportion of collagen regions(R²=0.5375,P<0.001)and the number of CD86-positive cells(R²=0.4345,P<0.001).Receiver operating characteristic(ROC)curve analysis demonstrated that the expression of BIK protein had certain predictive value for the survival prognosis of pancreatic cancer patients(AUC=0.7288,P=0.0034).In addition,BIK expression level was significantly correlated with lymph node metastasis(N stage)(P=0.001).Conclusions BIK is upregulated in pancreatic cancer and may promote tumor progression by promoting collagen deposition and inhibiting M1 macrophage infiltration,it is expected to be a promising prognostic biomarker and therapeutic target.